On April 3, 2020, the U.S. Food and Drug Administration (FDA) approved luspatercept-aamt (Reblozyl®) for the treatment of anemia failing an erythropoiesis-stimulating agent and requiring two or more red blood cell (RBC) units over eight weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).
Efficacy was demonstrated in the MEDALIST trial (NCT02631070), a randomized, multicenter, double-blind, placebo-controlled trial in 229 patients with Revised International Prognostic Scoring System very low-, low-, or intermediate-risk myelodysplastic syndromes who had ring sideroblasts and required RBC transfusions (two or more RBC units over eight weeks). Patients were randomized two to one to receive luspatercept-aamt or placebo. All patients received best supportive care, which included RBC transfusions.
The main efficacy endpoint in MDS-RS and MDS-RS-T was the proportion of patients who were RBC-transfusion independent (RBC-TI), defined as the absence of any RBC transfusion during any consecutive eight-week period between weeks 1 and 24.
Of the 153 patients who received luspatercept-aamt, 58 (37.9%; 95% CI = 30.2, 46.1) were RBC-TI for at least eight weeks, compared to 10 patients (13.2%; 95% CI = 6.5, 22.9) who received placebo (treatment difference = 24.6% [95% CI = 14.5, 34.6; p < 0.0001]).
The most common (> 10%) adverse reactions to luspatercept-aamt are fatigue, headache, musculoskeletal pain, arthralgia, dizziness or vertigo, nausea, diarrhea, cough, abdominal pain, dyspnea, and hypersensitivity.
The recommended starting dose of luspatercept-aamt is 1 mg/kg once every three weeks by subcutaneous injection. Review hemoglobin results prior to each administration.
FDA granted luspatercept-aamt orphan drug and fast-track designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.